Intraocular pressure is the result of a balance between aqueous humor formation and aqueous humor outflow against the tension of the ocular wall. This proposal will focus on the mechanisms by which aqueous humor is produced across the ciliary body. Fluid movement across a membrane essentially depends on two driving forces: hydrostatic pressure gradient and solute concentration gradient. In the in vivo systems these gradients are difficult both to measure and to control. In addition, they may influence each other, and can be influenced by local and systemic metabolic, circulatory and neurologic factors. In biological membranes metabolically driven fluid transport is a consequence of osmotic gradients produced and maintained by active ionic transport. The specific aim of this project is to study, in the isolated iris-ciliary body, ionic transport processes and fluid transport as they relate to aqueous humor formation. Studies will be performed in tissues obtained from rabbits, cats, monkeys and human autopsy eyes. Techniques to be applied include measurements of: 1) transepithelial electrical parameters; 2) unidirectional fluxes; 3) fluid transport; 4) media acidification and bicarbonate transport; 5) intracellular parameters with microelectrodes; 6) coupling of metabolism to ionic flows. The effect of relevant pharmacological agents (adrenergic agonists and antagonists, inophores, Na-K ATPase inhibitors, carbonic anhydrase inhibitors, c-AMP related agents, etc.) on all previously measured parameters will be investigated. It is expected to obtain a coherent and accurate description of the contribution of active transport and metabolic energy to the production of aqueous humor.